The term sterilization packaging unit refers to the package per se, i.e. without any content. For example, a sterilization packaging unit can be a so-called primary package which is a sealed or closed packaging system for enclosing the objects to be sterilized. The term packaging system refers to one or several packaging materials which are intended as part of or all of a primary package. The sterilization packaging unit can also be a so-called secondary package which is provided to accommodate one or several parts of objects to be sterilized, each one contained in its primary package. The term sterilization packaging unit is intended to refer in particular to an end-usage package. This relates to the package, in which in particular a medical product is sterilized. The end-usage package can be a primary package which is additionally provided with a secondary and/or transport package.
Many objects must be sterilized before they are used, particularly in the medical field, in order to kill microbes, i.e. viable microorganisms, on the objects. Such medical objects to be sterilized can be, for example, instruments, linen or liquids. Depending on the type of objects to be sterilized an appropriate physical or chemical sterilization method is used. In the medical field vapor sterilization methods are predominantly used. These are characterized by a high level of efficacy and environmental compatibility. In vapor sterilization methods sterilization is carried out with confined and saturated steam. The temperature of the steam is for example 121° C. or 134° C. Sterilization is carried out using autoclaves.
Furthermore, microbes can also be killed by high-energy ionizing beams or by an H2O2-based plasma. Chemical sterilization methods include sterilization by means of ethylene oxide or formaldehyde.
Medical objects to be sterilized are packaged for sterilization. It is possible for this purpose to use container packages, e.g. in the form of a box, paper packages in which the objects to be sterilized are wrapped in a number of layers of paper, and other packages. Paper packages which have a transparent casing are used in industry to pack sterile disposable material and in hospitals for individually packing disposable material or reusable goods. These packages can be in particular packages based upon transparent bags and transparent tubes consisting of paper and synthetic composite sheeting. The package serves to ensure the sterility achieved by the sterilization method until the sterilized objects are used. They can be stored in hospitals for a period of weeks to several months.
The quality requirements for the sterilization method are high. Under WHO guidelines and various European pharmacopoeia, out of 1000000 “sterile” products 999999 must be sterile. This requirement forms the substantial content of the European Standard EN 556-1:2001.
The sterilization method itself is typically evaluated and standardized with physical-chemical and microbiological parameters. A known and reliable method for testing the efficacy of a sterilization method consists of subjecting a test microbial unit to the sterilization method to be tested, at the same time as the objects to be sterilized. This test microbial unit is formed by a number of microbes which are particularly resistant to the sterilization process and which are enclosed as a unit by a casing. After the sterilization process this test microbial unit is opened under sterile conditions and tested to see if the microbes contained therein are capable of multiplying. If the sterilization process has taken place correctly no multiplication of the test microbes will take place since these test microbes have been killed by the sterilization. The test microbes therefore represent an indicator for the effectiveness of the sterilization method.
A test microbial unit of this type is provided in particular in the form of self-developing bio-indicators (available from the company 3M Medica, branch of 3M Deutschland GmbH, Neuss, Germany). They comprise an ampoule, containing nutrient medium, and a plastic casing, in which the ampoule and spores of a defined microbe type are located. The plastic casing comprises a closure having a vapor-permeable, but microbe-tight filter. The bio-indicators are subjected to the sterilization process which is to be tested. The ampoule is then crushed. As a consequence, the microbes and the nutrient medium are mixed together. The indicator is then incubated in the incubator and is evaluated in terms of a change in color of the nutrient medium. If there is no change in color, no microbial growth has taken place. In this case, the sterilization method has been efficient and has killed the microbes of the bio-indicator. A similar indicator is also available from the company gke-mbH, Waldems-Esch, Neuss, Germany. However, the design of indicators of this type means that they cannot be used to test whether, after successful sterilization, any recontamination of the sterilized objects has occurred during a specific period of storage.
There are also quality standards for the packaging material. These generally relate to partial aspects of the sterilization packaging unit such as material properties, sealing tightness of closures etc.
On the one hand, the so-called microbial barrier of the sterilization packaging unit used is a factor in the recontamination of the sterilized objects. This microbial barrier is the ability of the sterilization packaging unit to prevent the entry of microorganisms. On the other hand, various external influences such as the type of storage or transportation and mechanical stressing on the packaged sterilized objects and ambient influences such as air flow, microbial content of the air and fluctuations in air pressure are factors in recontamination.
A known device for testing the microbial barrier quality of partial components of a container package is formed in such a manner that it generates a negative pressure in one container via orifices provided in a cover of the container (EN 868-1, Appendix G). By means of this negative pressure the tightness of a seal between the cover and the container body can be tested. However, this is merely a device for a specific physical testing method for packages which are in the form of containers. This method relates merely to the seal between the body and the cover but not the microbial barrier of the vapor orifices such as filters and valves. Furthermore, ambient influences, e.g. microbial content of the air, are not included in this testing method. This device can therefore give no reliable evidence as to the extent to which recontamination of sterilized objects in the sterilization packaging unit must be expected.
Furthermore, there is a microbiological DIN testing device (DIN 58953, Part 6) which is provided to test sterilization paper. In this device a microbial penetration testing unit in the form of a glass laboratory flask is closed with the sterilization paper to be tested and is tested to see whether, by cooling the air in the microbial penetration unit, an air flow passes into the glass laboratory flask and carries particles containing microbes through the sterilization paper when the paper has been coated with a powder containing a defined microbe count of Bacillus-subtilis spores prior to cooling. Provision is made to heat the glass laboratory flask to 50° C. and to cool it to 10° C. repeatedly and consecutively. Spores which may enter the glass laboratory flask through the sterilization paper are observed and evaluated by microbiological means using incubation of the glass laboratory flask containing nutrient medium. This testing method, however, does not relate to a sterilization packaging unit as a whole but only to paper which is used as a packaging material. This is purely a material test in which, apart from the application of the powder, no further ambient influences are included.
From the publication by de Bruijn, A.C.P. and Kastelein, J., Einfach-oder Mehrfach-Verpackung von Medizinprodukten: Verfahrensbewertung durch Forschung, Zentralsterilisation; 1999; 7 (5): 292-303 a device is known with which the filtering effect of a package with respect to an aerosol consisting of 1.0•m latex particles is determined by means of a particle counter (cf. loc, cit., 3., page 297, para. 1). The known method is not intended, and is not suitable for testing packages in the form in which they are used in order to determine their capability to maintain sterility under hospital practice conditions. In particular, the method forming the basis of the device is not based on the determination of the relevant end point, namely the detection of microbiological contamination.
From the American Society for Testing and Materials (ASTM) designation F 1608-00 describes a method which serves to determine the microbial penetration or barrier efficacy of porous materials such as paper: a microbe-containing aerosol including Bacillus subtilis-spores is introduced into a chamber by means of an atomizer. By the intermediate placement of the test material on to filter carriers and a further microbe-tight filter membrane, it is possible to determine the microbial penetration of the test body during a defined passage of a microbe-containing aerosol. In this case, it is a device for testing material used for packaging purposes but not a device for examining a sterilization packaging unit which is typically used in practice.
It is also known to test some of the sterilized objects for recontamination after a certain period of time by means of random sampling. However, a disadvantage of this is the fact that to do this the sterilization packaging unit needs to be opened and, during the test itself, microbes can reach the object being tested so that the result of the test can thereby be rendered erroneous. However, this method is not practicable for hospital use so that it is not routinely used in hospitals.
From the publication by Junghannβ U., Winterfeld S., Gabele L., Kulow U., Hygienisch-mikrobiologische and technische Überprüfungen von Sterilisier-Containersystemen, Zentralsterilisation 1999; 7 (3): 154-162 a device is known for testing sterilization containers in the form of packaging containers. This device consists of a test chamber, into which the containers to be tested can be inserted. Before they are placed in the test chamber the containers were fitted with the associated filters and sterilized. The containers were then provided with solid nutrient medium in Petri dishes and closed. A microbe-containing aerosol was introduced into the interior of the test chamber using a spray bottle. By means of a connection fitting fitted to the containers to be tested prior to introduction into the test chamber, suction was carried out through the containers to be tested, by means of a hose pump. After the suction the containers were opened again and the solid nutrient medium dishes were removed. These were then incubated to test for microbes on the solid nutrient medium. The colony-forming units (cfu) were then counted.
The known device is not suited to testing an end-usage package in the form in which it is used in practice, in order to test its barrier efficacy with respect to recontamination. It is rather the case that the containers need to be provided with a suction fitting before being introduced into the known test chamber. Furthermore, after the containers have been in contact with the aerosol in the test chamber, they must be removed from the test chamber and opened in order to remove the solid nutrient medium dishes and to incubate them in a separate apparatus. The container cannot therefore remain in an undisturbed condition until the results of the test are evaluated. External sources of errors can therefore not be ruled out during the test. It is rather the case that the removal of the solid nutrient medium dishes for subsequent incubation is associated with a risk of contamination and therefore with the risk of imprecise measurement. According to Junghannβ et al. only a difference value for the microbial barrier is determined but no absolute value is obtained. In the known testing arrangement no evidence as to sterility could be obtained because of the non-sterile handling of the solid nutrient medium.
In the European Standard EN 868-1 of 1997 it is stated under point 4.6 that there was no suitable end-usage package testing method which is standardized. Also there is still no such method in place at the present time. Therefore, in “ASTM-Standard Guide for Design and Evaluation of Primary Packaging for Medical Products” of 2001 (Designation: F 2097-01) it is noted under point 4.6.2 that no individual testing method could completely predict the efficiency of the end-usage package.
To date, only one method has been proposed which is suitable for testing the packaging as a whole or a sterilization packaging unit in use, for its efficacy in preventing recontamination of the sterilized objects in the period of time between sterilization and usage thereof (Dunkelberg, H. und Wedekind, S., Hygiene+Medizin, 27th year, 2002-Suppl. 1, 29 Rekontamination von papierverpackten Sterilgutpaketen unter mechanischer Belastung; Dunkelberg, H. und Wedekind, S., Biomedezinische Technik, 47 (2002), 290-293, Eine neue Methode zur Wirksamkeitsprüfung von Sterilisiergutverpackungen in der Praxis). Using this method which is the subject of the pending German patent application 102 13 361.1, it is also possible to detect any recontamination of the sterilized objects which has possibly taken place. In the case of this known method of testing a sterilization packaging unit provided for the sterilization of objects to be sterilized, in particular medical objects to be sterilized, for its efficacy in preventing microbial recontamination of the sterilized objects after they have been sterilized, the following steps are provided: The sterilization packaging unit is charged with nutrient medium, e.g. nutrient agar-filled dishes. The sterilization packaging is then subjected to a sterilization process and subsequently is stored for a period of time under ambient conditions, wherein immediately after the sterilization process it is fundamentally possible that microbes will become established in the nutrient medium. Subsequently, the sterilization packaging unit is subjected to conditions in which microbes multiply for cultivation of microbes which are present in or on the nutrient medium. Finally, the sterilization packaging unit is opened and microbes, which have multiplied in or on the nutrient medium, are observed.
In the case of this known method, the nutrient medium is ready to use immediately after the sterilization process. Even at this point in time, it is possible for microbes to become established and multiply in or on the nutrient medium. The period of time, during which a nutrient medium can be used as a basis for a multiplication of microbes is limited as a result of the unavoidable water loss and amounts to a maximum of two to three weeks e.g. for solid nutrient medium. Therefore, in the case of the known method, the point in time at which effected recontamination can be observed is predetermined to a limited extent by the limited shelf life of the nutrient medium.
Furthermore, a device is known which can be used in particular for carrying out the method in accordance with patent application 102 13 361.1 which is suitable for testing the package as a whole (Dunkelberg, H., Zietz, B., Wedekind, S., The Society for Healthcare Epidemiology of America, 13th Annual Scientific Meeting, Preliminary Results for a New Final Package Test to Assess the Quality of Sterile Package Systems). In this case, the ambient conditions can be fixed such that the sterilization packaging unit to be tested is subjected for a specific period of time to a very high microbial density which does not normally occur in the environment of stored packaging units.